Diabetes mellitus is one of the most frequently occurring chronic illnesses worldwide. Diabetes mellitus is caused by a malfunction of the regulation of the carbohydrate metabolism. In this case, the insulin production by the β-cells in the pancreas is suppressed (type I diabetes) or abnormal (type II diabetes). Approximately 10-15% of diabetic patients are to be assigned to type I diabetes, which require externally supplied insulin for the breakdown of the blood glucose. The larger proportion of type II diabetic patients typically do not require externally supplied insulin. These patients may combat the metabolic illness with the aid of diet and orally supplied medications. The current treatment of type 1 diabetic patients comprises the administration of insulin doses through multiple subcutaneous insulin injections during the day. Measuring the blood sugar concentration is required to determine the dose before the administration of the insulin syringe. This is typically performed manually by the patient, usually by taking a blood drop at the fingertip and supplying it to a measuring device. The insulin dose is adapted to the current blood sugar value and administered subcutaneously in the form of a bolus injection.
An increasing number of type I diabetic patients also use insulin pumps, which deliver insulin continuously and thus simulate the natural function of the pancreas better. Insulin pumps of this type may also be implanted completely. With this type of therapy, extracorporeal glucose measurement is nonetheless necessary to be able to adapt the insulin dose accordingly.
Nonetheless, with the forms of insulin therapy used currently, one frequently exceeds or falls below the desired blood sugar level. A continuously elevated blood sugar concentration (hyperglycemia) results in the development of later diabetic complications, such as microangiopathy, neuropathy, and macroangiopathy. Falling below the normal blood sugar concentration (hypoglycemia) represents an extremely frequent acute complication in the treatment of insulin requiring diabetes. The consequences of hypoglycemia particularly relates to the central nervous system, since glucose is the main nutrient of the brain. The most important goal in insulin therapy is avoiding severe hypoglycemia but also reducing the late complications due to hyperglycemia. In order to be able to keep the blood sugar concentration continuously in a narrow target range, frequent measurements of the blood sugar are absolutely necessary in connection with the administration of appropriate insulin doses. The development of continuous glucose measurement methods is being worked on intensively to allow frequent or even continuous blood sugar measurement.
The goal is the development of an artificial endocrine pancreas which regulates the administration of insulin automatically on the basis of the measured blood sugar concentration. Because of stability problems with implanted glucose sensors, until now no artificial pancreases of this type have been able to be developed. However, the newest sensors for continuous measurement of the glucose concentration show improvements with regard to long-term stability, so that these types of support devices may be available for the treatment of type I diabetes in the foreseeable future.
A completely implantable artificial pancreas is described in U.S. Pat. No. 5,298,022 A, the blood sugar being ascertained via a microdialysis arrangement. The result of the blood sugar measurement is transmitted wirelessly to an insulin pump, which sets the insulin quantity to be delivered in accordance with the measured blood sugar value.
U.S. Pat. No. 6,558,351 B1 describes a device of the representational type, the sensor for measuring the tissue glucose concentration being positioned at a location of the body and the measured values being transmitted through telemetry to a unit for delivering the insulin, which is positioned at another location of the body. A problem in the measurement of the tissue glucose concentration is generally the conclusion of the blood glucose concentration, according to which the insulin quantity to be delivered is to be regulated. In addition, the arrangement of two catheters in the subcutaneous tissue for the measurement of the tissue glucose concentration and the delivery of the insulin is complex and stressful for the patients.
U.S. Pat. No. 6,770,030 B1 describes a catheter, using which measurement of the glucose concentration and delivery of insulin are possible simultaneously. However, there is a spatial separation between the insulin delivery unit and the glucose sensor in this type of catheter.
EP 1,166,808 A2 discloses an injection needle unit usable in a portable automatic syringe device, the injection needle unit comprising a feeding tube, an “L”-shaped injection needle member connected to one end of the feeding tube, a connector connected to the other end of the feeding tube, and a depressing member integrally formed with the injection needle member in such a fashion that the injection needle protrude perpendicularly from the depressing member, the depressing member being depressed against the skin of a user upon penetrating the injection needle member into the subcutaneous tissue of the user. The injection needle unit comprises a glucose sensor attached to the injection needle and adapted to penetrate the body of the user when the injection needle penetrates the body of the user. The glucose sensor comprises an electrode wire wound around an injection needle in the form of a core, an insulating layer coated over the injection needle to insulate the injection needle from the electrode wire, and an enzyme member fitted around a portion of the injection needle adjacent to the injection tip while being insulated from the electrode wire. The enzyme member and the electrode wire penetrating the body of the user when the injection needle penetrates the body of the user, and leads connected to the enzyme member and the electrode wire, respectively, to electrically connect the enzyme member and the electrode wire to a voltage sensing means included in the automatic syringe device.
U.S. Pat. No. 6,017,318 discloses a feedback controlled drug delivery system including the automated sampling and analysis of a patient sample and dosing the patient based on the analysis. Automated sampling may be performed by direct analysis of the patient sample, such as for the measurement of a blood sample coagulation state or a glucose level. The drug delivery system includes a sample set that has a bidirectional patient tube that allows for delivery of the patient sample to an analyzer, and at another time, the infusion of a therapeutic drug. A controller receives a measurement from the analyzer, and based on that measurement, adjusts the delivery of the therapeutic fluid. The sample set has a quick-clear Leur fitting that allows for more effectively clearing a first fluid from a Leur fitting when starting a second fluid. The system also has a reagent cassette holder that protects, using a foam gasket, a reagent on a sample slide. Further, the system provides an interlock apparatus that assures a sample tube is occluded by either or both a slide clamp and by a platen arm compressing the sample tube to a peristaltic pump.
JP 2004-283378 discloses a drug injector provided with a syringe storing insulin, a motor quantitatively guiding the insulin, an injection needle injecting the insulin guided from the syringe by the motor in the body of the patient, the sensor measuring the glucose concentration in the body of the patient and a microcomputer controlling an injection speed or an injection timing of the insulin to be guided by the motor based on the concentration measured by the sensor. This device is so constituted that the sensor and the injection needle are dipped in the glucose of the known quantity and concentration, the fixed quantity of the insulin is injected from the injection needle by the motor to dilute the glucose, and its concentration in the diluting process is measured by the sensor to adjust the sensor.
U.S. Pat. No. 5,097,834 discloses a process for determining parameters of interest in living organisms. For this purpose, a perfusion fluid is directly introduced in the tissues. After its partial balancing of the tissue parameter of interest, the perfusion fluid is collected and analyzed for the parameter of interest, as well as for endogenous or exogenous marker properties indicative of the degree of interaction between the perfusion fluid and the tissue in such a way that the parameter of interest can be determined with the help of such characteristic properties.
There may be a need for an efficient device and an efficient method for the delivery of a physiologically active substance in dependence of a measured physiological parameter.